• Title/Summary/Keyword: FAS1

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Study on Synergistic Anti-tumor Effect of Combination with Adriamycin and Palginhonhapwhajucwhan (팔진탕합화적환(八珍湯合化積丸)과 Adriamycin의 병용처리시 나타나는 synergistic 항종양(抗腫瘍) 효과(效果)에 관(關)한 작용기전 연구(硏究))

  • Moon, Gu;Moon, Seok-Jae;Won, Jin-Hee;Cho, Jung-Yun;Park, Sang-Gu;Song, Bong-Gil;Park, Rae-Gil;Lee, Byung-Gu
    • The Journal of Internal Korean Medicine
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    • v.21 no.3
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    • pp.443-452
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    • 2000
  • Objective : This study was designed to evaluate the synergistic effect on cytotoxicity of combination with adriamycin and Palginhonhapwhajucwhan, a traditional prescription for cancer treatment in oriental medicine, in Chang, HL-60, Hep-3B and Alexander cells. Methods : We observed cell viability in Chang, HL-60, Hep-3B, and Alexander cells by crystal violet staining. Those cells were treated with various concentrations of adriamycin alone, Palginhonhapwhajucwhan alone and combination of two medications for 10 hr. On condition of $0.5{\mu}l/ml$ adriamycin alone, $15.6{\mu}l/ml$ Paljintanghapwhajucwhan alone and combination of two medications, at first, we observed colony forming of Chang and HL-60 cells. Second, we observed DNA fragmentation by agarose electrophoresis in Chang, HL-60, Hep-38 and Alexander cells. Third, we measured the catalytic activation of caspase-1, 2, 3, 6, 8, and 9 protease in Chang cells and caspase-3 protease in Chang, HL-60, Hep-3B and Alexander cells by using fluorogenic substrate. Finally, we isolated mRNA of Fas in Chang, HL-60, Hep-38 and Alexander cells and observed that Fas gene was amplified by RT-PCR Results : 1. The combination of adriamycin and Palginhonhapwhajucwhan synergistically augmented the cytotoxicity of Chang and HL-60 cells whereas did not in Hep-38 and Alexander cells. 2. Cotreatment of two drugs also markedly inhibited the colony forming ability both in Chang and HL-60 cells. 3. The cytotoxicity of these medicatons was revealed as apoptosis characterized by high molecular wight DNA fragmentaton. 4. The apoptotic cytotoxicity was mediated by activation of caspase-3 protease in Chang cells. 5. Synergistic increase in apoptotic cytotoxicity by combination of two medications was dependent on the expression of Fas in cancer cells. Conclusions : Combination of adriamycin and Palginhonhapwhajucwhan significantly augmented apoptotic cytotoxicity of Fas-positive cells such as Chang and HL-60 cells via acticaton of apoptosis signaling pathway.

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Alkaloids from Beach Spider Lily (Hymenocallis littoralis) Induce Apoptosis of HepG-2 Cells by the Fas-signaling Pathway

  • Ji, Yu-Bin;Chen, Ning;Zhu, Hong-Wei;Ling, Na;Li, Wen-Lan;Song, Dong-Xue;Gao, Shi-Yong;Zhang, Wang-Cheng;Ma, Nan-Nan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9319-9325
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    • 2014
  • Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted much attention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5, 6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted, analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cells HepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilical vein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 was the most sensitive to AHL treatment, a very low dose ($0.8{\mu}g/ml$) significantly inhibiting proliferation. The non-tumor cell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored. We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interrupt polymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1, was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 was observed as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis of HepG-2 cells.

Prediction of Affinity between Membrane and Esters Using Solubility Parameter (용해도 파라미터에 의한 막과 esters 간의 친화도 예측)

  • Song, Kun-Ho;Lee, Kwang-Rae
    • Membrane Journal
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    • v.24 no.6
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    • pp.484-490
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    • 2014
  • To find out the feasibility of the separating/enriching esters from aqueous solution using FASs (Fluoloalkyl-silanes-coupling agent)-surface modified hydrophobic membrane, the solubility parameter of FASs was obtained and compared with those of esters and water. The value of the solubility parameter of FASs (${\delta}_t=16.9$) was almost same with those of esters (ethyl acetate ${\delta}_t=18.1$, propyl acetate ${\delta}_t=18.0$, ethyl propionate ${\delta}_t=17.9$, butyl acetate ${\delta}_t=17.4$, ethyl butyrate ${\delta}_t=17.0$). However, the calculated value of the solubility parameter of water was ${\delta}_t=47.8$, which was far from the value of the solubility parameter of FASs (${\delta}_t=16.9$). This means that the FASs-modified membrane has a much higher affinity to esters than water. The experimental results of permeation flux of esters used in this study showed that the order of permeation flux predicted by the solubility parameter was almost coincide with experimental results. It might be concluded that the solubility parameter may be applicable for a separating/enriching flavors from aqueous natural-flavor solution, in which esters are main components of natural flavors.

Dietary supplementation of finishing pigs with the docosahexaenoic acid-rich microalgae, Aurantiochytrium limacinum: effects on performance, carcass characteristics and tissue fatty acid profile

  • Moran, Colm A.;Morlacchini, Mauro;Keegan, Jason D.;Fusconi, Giorgio
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.5
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    • pp.712-720
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    • 2018
  • Objective: The aim of this experiment was to evaluate the effect of dietary supplementation with the docosahexaenoic acid (DHA)-rich microalgae, Aurantiochytrium limacinum (AURA) on pig performance, carcass traits, and the fatty acid composition of pork Longissimus lumborum (LL) and backfat. Methods: A total of 144 Pig Improvement Company (PIC)${\times}$Goland finishing pigs (72 females and 72 castrated males) of mean weight 117.1 (${\pm}13.1$) kg were blocked by sex and body weight and provided with 0% or 1% AURA in isonutritive and isocaloric diets. A total of 24 pens provided 12 replicates per treatment. Animals were weighed on day 0 and 28 with feed and water intake recorded per pen. After 31 days supplementation (28 days of study and 3 days until the slaughtering date) three animals per pen (n = 72) were slaughtered and the LL and backfat thickness, lean meat content and dressing percentage were recorded for the carcasses. The fatty acid (FA) profile of the LL and backfat was established by direct FA methyl ester synthesis. Results: No differences were observed for any performance parameters or carcass traits. Supplementation with AURA resulted in significant changes to the FA profiles of both the LL and backfat with male and female pigs responding differently to supplementation in terms of particular FAs. Overall, pork LL samples had significantly higher eicosapentaenoic acid (p<0.001) and DHA concentrations (p<0.001), and higher omega-3 (n-3) FAs (p<0.001), as well as an increased omega3:omega6 (n-3:n-6) ratio (p = 0.001). For backfat, supplementation resulted in significantly higher amounts of DHA (p<0.001) and n-3 FAs (p<0.001). Conclusion: These results indicate that dietary supplementation with 1% AURA over a 31 day period can increase the FA composition of pork LL and backfat, specifically the DHA, with no major impact on growth performance and carcass traits.

Effects of Agastachis Herba Extract and Lysimachiae Herba Extract on the Experimental Cellular Model of NFLDs Induced by Palmitic Acid (곽향과 금전초 추출물이 Palmitic acid로 유발된 비알코올성 지방간 세포 모델에 미치는 영향)

  • Lee, Hye-in;Kim, Young-kwang;Lim, Hyeon-chan;Lee, Da-eun;Kim, Eun-ji;Moon, Young-ho
    • The Journal of Internal Korean Medicine
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    • v.39 no.3
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    • pp.302-312
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    • 2018
  • Objectives: This study was performed to investigate the effects of two herbal medicines, Agastachis Herba and Lysimachiae Herba, on a cellular model of non-alcoholic fatty liver diseases (NFLDs). Methods: HepG2 cells were treated with palmitic acid and with various concentrations of Agastachis Herba (AH) or Lysimachiae Herba (LH) extract in water. The lipotoxicity was assessed using EZ-cytox, and the lipoapoptosis was assessed using cell death detection ELISA. Intracellular lipids were measured by oil red O staining. The efficacy of AH and LH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in HepG2 cells was measured by reverse transcription polymerase chain reaction (RT-PCR). Results: Both AH and LH extracts increased lipoapoptosis and decreased lipotoxicity and levels of SREBP-1c, ACC, and FAS (SREBP-1c, ACC, and FAS are factors in lipid synthesis). In the oil red O staining experiment, both extracts also reduced intracellular lipid accumulation; in this instance, LH's efficacy was superior to that of AH. Conclusions: According to the results, both AH and LH are likely to contribute to non-alcoholic fatty liver disease, as both interfere with lipid synthesis.

Implication of Angiogenesis and Expression of VEGF in Follicular Thyroid Tumor (여포상 갑상선종양에서 신생혈관형성 및 혈관내피성장인자(VEGF)의 발현의 의의)

  • Ryu Ki-Sun;Soh Euy-Young;Yim Hyun-Ee;Kim Myung-Wook
    • Korean Journal of Head & Neck Oncology
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    • v.14 no.1
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    • pp.70-75
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    • 1998
  • Tumor growth and metastasis depends on angiogenesis. Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells in vitro and promotes neoangiogenesis in vivo. Objective: Follicular thyroid cancers(FTC) are a vascular tumor and traditionally metastasize via blood vessels. Likely other cancers, angiogenesis may playa important role in FTC. We, therefore, investigated the expression of VEGF and microvascular density by immunohistochemistry in FTC and follicular adenoma(FA). Materials and Methods: Findings of immunohistochemical stainings for VEGF and CD31 were measured by grading scale from +1 to 4+(strongest) and by counting the stained microvessels in 14 FTCs and 14 FAs. Results: 1) Expression of VEGF. a) FTCs have stronger expression than FAs in areas of tumor adjacent to capsule($mean{\pm}SD\:\;3.2{\pm}0.9\;vs\;2.0{\pm}0.9$, p<0.01) and in central area($2.3{\pm}0.7\;vs\;1.3{\pm}0.6$, p<0.01). b) The VEGF expression of capsular area in FTCs are higher than that of central area(p<0.05). 2) Microvascular density by CD31. a) FTCs have more microvessels than FAs in areas of adjacent to capsule($78.9{\pm}27.3\;vs\;38.7{\pm}15.6$, p<0.01) and in central area($75.5{\pm}23.3\;vs\;27.8{\pm}10.7$, p<0.01). b) In FTCs, the number of microvessels of capsular area are more than that of central tumor area, but not significant statistically(p>0.05). Conclusion: The higher expression of VEGF and microvascular density in FTC suggests angiogenesis plays an important role in progression of FTC.

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Use of Lipid Extracts from Various Oil Grains to Supply Dietary Omega-3 Fatty Acids for Dairy Foods - A Preliminary Study

  • Jin, Long;Sim, Jeong Seok;Song, Kwang-Young;Kim, Dong-Hyeon;Chon, Jung-Whan;Kim, Hyunsook;Seo, Kun-Ho
    • Journal of Dairy Science and Biotechnology
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    • v.36 no.1
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    • pp.32-38
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    • 2018
  • The objective of this research was to determine the grain oil most suitable for the production of omega-3 fatty acids (FAs) in China, in order to supply dietary omega-3 FAs. This study focused on the nutritional significance of omega-3 FAs and the wide search of sources of dietary omega-3 FA from oil grains produced in China. Five oil grains produced in the Yanbian region, namely sesame, flax, peanut, soybean, and corn, were selected and analyzed for their fat content and FA composition. Results showed that the lipid content in sesame, flax, and peanut, which was more than 30%, was higher than that in soybean and corn. The polyunsaturated FA content was found to be directly proportional to omega-3 FA content. Flax showed a considerably higher omega-3 FA content (53.43%) than other samples, suggesting its potential as a source of dietary omega-3 FA. The optimal daily intake of flax for males and females was determined to be 2.99 g (over one table spoon) and 2.06 g (nearly one table spoon), respectively. Flax showed the lowest ratio of omega-6 and omega-3 FA (0.32%), which can help reduce this ratio in the human body; the intake of equal amounts of flax and corn could achieve an optimum ratio of 1:1. These results can prove to be valuable in the preparation of various functional dairy foods in the future.

Apoptosis of Human Jurkat T Cells Induced by the Methylene Chloride Extract from the Stems of Zanthoxylum schinifolium is Associated with Intrinsic Mitochondria-Dependent Activation of Caspase Pathway (인체 급성백혈병 Jurkat T 세포에 있어서 Zanthoxylum schinifolium 줄기의 methylene chloride 추출물에 의해 유도되는 세포자살기전 규명)

  • Jun, Do-Youn;Woo, Mi-Hee;Park, Hae-Sun;Kim, Jun-Seok;Rhee, In-Koo;Kim, Young-Ho
    • Journal of Life Science
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    • v.18 no.11
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    • pp.1499-1506
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    • 2008
  • To examine antitumor activity of the edible plant Zanthoxylum schinifolium, the cytotoxic effect of various organic solvent extracts of its stems on human acute leukemia Jurkat T cells was investigated. Among these extracts such as methanol extract (SS-7), methylene chloride extract (SS-8), ethyl acetate extract (SS-9), n-butanol extract (SS-10), and residual fraction (SL-11), SS-8 exhibited the most cytotoxic activity against Jurkat T cells. The methylene chloride extract (SS-8) possessed the apoptogenic activity capable of inducing sub-G1 peak along with apoptotic DNA fragmentation in Jurkat T cells. Western blot analysis revealed that SS-8 induced apoptosis via mitochondrial cytochrome c release into cytoplasm, subsequent activation of caspase-9 and caspase-3, and cleavage of PARP, which could be blocked by overexpression of Bcl-xL. Jurkat T cell clone I2.1 $FADD^{-/-}$) and Jurkat T cell clone I9.2 (caspase-$8^{-/-}$ were as sensitive as was the wild-type Jurkat T cell clone A3 to the cytotoxic effect of SS-8, suggesting no contribution of Fas/FasL system to the SS-8-mediated apoptosis. The GC-MS analysis of SS-8 showed that it was composed of 16 ingredients including 9,12-octadecanoic acid (18.62%), 2,4-dihydro-5-methyl-4- (1-methylethylidene)- 2-(4-nitrophenyl)-3H- pyrazol-3-one (14.97%), hexadecanoic acid (14.23%), (z,z)-6,9-pentadecadien- 1-ol (13.73%), 5,6-dimethoxy-2-methyl benzofuran (10.95%), and 4-methoxy-2-methylcinnamic acid (5.38%). These results demonstrate that the methylene chloride extract of the stems of Z. schinifolium can induce apoptotic cell death in Jurkat T cells via intrinsic mitochondria-dependent caspase cascade regulated by Bcl-xL without involvement of the Fas/FasL system.

Condurango (Gonolobus condurango) Extract Activates Fas Receptor and Depolarizes Mitochondrial Membrane Potential to Induce ROS-dependent Apoptosis in Cancer Cells in vitro -CE-treatment on HeLa: a ROS-dependent mechanism-

  • Bishayee, Kausik;Mondal, Jesmin;Sikdar, Sourav;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.18 no.3
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    • pp.32-41
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    • 2015
  • Objectives: Condurango (Gonolobus condurango) extract is used by complementary and alternative medicine (CAM) practitioners as a traditional medicine, including homeopathy, mainly for the treatment of syphilis. Condurango bark extract is also known to reduce tumor volume, but the underlying molecular mechanisms still remain unclear. Methods: Using a cervical cancer cell line (HeLa) as our model, the molecular events behind condurango extract's (CE's) anticancer effect were investigated by using flow cytometry, immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Other included cell types were prostate cancer cells (PC3), transformed liver cells (WRL-68), and peripheral blood mononuclear cells (PBMCs). Results: Condurango extract (CE) was found to be cytotoxic against target cells, and this was significantly deactivated in the presence of N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), suggesting that its action could be mediated through ROS generation. CE caused an increase in the HeLa cell population containing deoxyribonucleic acid (DNA) damage at the G zero/Growth 1 (G0/G1) stage. Further, CE increased the tumor necrosis factor alpha ($TNF-{\alpha}$) and the fas receptor (FasR) levels both at the ribonucleic acid (RNA) and the protein levels, indicating that CE might have a cytotoxic mechanism of action. CE also triggered a sharp decrease in the expression of nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) both at the RNA and the protein levels, a possible route to attenuation of B-cell lymphoma 2 (Bcl-2), and caused an opening of the mitochondrial membrane's permeability transition (MPT) pores, thus enhancing caspase activities. Conclusion: Overall, our results suggest possible pathways for CE mediated cytotoxicity in model cancer cells.